Nevus unius lateris, bilateral linear epidermal nevi, and ichthyosis hystrix may all be considered clinical variants of epidermal nevi. They were found in ten of 12 patients examined to be accompanied by congenital skeletal disorders. Five of these patients also had central nervous system (CNS) disease and two had other uncommon abnormalities including a conjunctival fibroma and hepatosplenomegaly. The high frequency of associated abnormalities of bone and CNS in this study as well as the frequent reports of such findings in the literature strongly suggests the possibility that extensive epidermal nevi form part of a syndrome including skeletal and CNS abnormalities. The presence of extensive epidermal nevi should be considered an indication for careful history and examination of the entire patient.